Sodium Hydroxide → (S)-2-((S)-2-((tert-Butoxycarbonyl)amino)-4-methylpentanamido)-4-methylpentanoic acid

HRID 849686Notes

Reaction equation

HRID 849686 reaction equation
[OH-].[Na+].[NH:3]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:4]([C:9]([NH:11][C@H:12]([C:17]([O:19]C)=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[CH2:5][CH:6]([CH3:8])[CH3:7]>O.CC(C)=O>[NH:3]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:4]([C:9]([NH:11][C@H:12]([C:17]([OH:19])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[CH2:5][CH:6]([CH3:8])[CH3:7]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 7073357Boc-leu-leu-ome

Product 1

HCID 7019882(S)-2-((S)-2-((tert-Butoxycarbonyl)amino)-4-methylpentanamido)-4-methylpentanoic acid

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent2×

Procedure

A solution of NaOH (1.34 g, 33.5 mmol) in water (15.0 g) was added dropwise over 10 min to the solution of Boc-Leu-Leu-OMe (10.0 g, 27.9 mmol) in acetone (20.0 g) and water (50.0 g) at 18-22° C. The reaction mixture was stirred at this temperature for 1 h and then analyzed by HPLC. When the methyl ester is under 5%, the reaction stirred for an additional 0.5 h. A white turbidity formed by the end of the reaction which was removed by filtration and rinsed with water (5.0 g). The clear filtrate was treated with formic acid (ca 0.8 g) to form a cloudy solution followed by immediate crystallization of product. Additional formic acid (1.5 g) was added (to pH 4.0-4.5) and the resulting product was collected by filtration then was washed by a mixture of acetone (10.0 g) and water (40.0 g). The solid product was suspended in a mixture of acetone (14.0 g) and water (56.0 g) for 15 min. The solid was collected by filtration and washed with a mixture of acetone (7.5 g) and water (30.0 g) and dried in vacuo at 45° C. Yield: 8.6-8.8 g (89.6-91.7%).

Workup

  1. stirringthe reaction stirred for an additional 0.5 h
  2. customA white turbidity formed by the end of the reaction which
  3. customwas removed by filtration
  4. washrinsed with water (5.0 g)
  5. additionThe clear filtrate was treated with formic acid (ca 0.8 g)
  6. customto form a cloudy solution
  7. customfollowed by immediate crystallization of product
  8. additionAdditional formic acid (1.5 g) was added (to pH 4.0-4.5)
  9. filtrationthe resulting product was collected by filtration
  10. washthen was washed by a mixture of acetone (10.0 g) and water (40.0 g)
  11. additionThe solid product was suspended in a mixture of acetone (14.0 g) and water (56.0 g) for 15 min
  12. filtrationThe solid was collected by filtration
  13. washwashed with a mixture of acetone (7.5 g) and water (30.0 g)
  14. customdried in vacuo at 45° C

Sources & evidence

ORD record
ord-daadedd99c344bc08d3af91444ad3098
Source dataset
uspto-grants-2000_01
Patent number
US06013764

Reaction notes

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